Rhesus monkey TRIM5α protein SPRY domain contributes to AP-1 activation

Lei, Na; Tang, Yan-Dong; Wang, Cuihui; Liu, Cong; Wang, Xiaojun

doi:10.1074/jbc.ra117.000127

Cited by 7 publications

(3 citation statements)

References 71 publications

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“…the NF-κB reporter under basal conditions, which is consistent with previous studies from us and others 38,39,46 , these proteins negatively regulated TNFα-mediated NF-κB activation, as seen with huTRIM5α (Fig. 9e).…”

Section: Conserved Suppression Effects Of Nonhuman Trim5α and Trimcyp...supporting

confidence: 92%

TRIM5α recruits HDAC1 to p50 and Sp1 and promotes H3K9 deacetylation at the HIV-1 LTR

Ran

Zhu

et al. 2023

Nat Commun

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Tripartite motif-containing protein 5α (TRIM5α) is generally known to block the postentry events of HIV-1. Here, we report an uncharacterized role for TRIM5α in the maintenance of viral latency. Knockdown of TRIM5α potentiates the transcription of HIV-1 in multiple latency models, which is reversed by shRNA-resistant TRIM5α. TRIM5α suppresses TNFα-activated HIV-1 LTR-driven as well as NF-κB- and Sp1-driven gene expression, with the RING and B-box 2 domains being the essential determinants. Mechanistically, TRIM5α binds to and enhances the recruitment of histone deacetylase 1 (HDAC1) to NF-κB p50 and Sp1. ChIP‒qPCR analyses further reveal that the association of TRIM5α with HIV-1 LTR induces HDAC1 recruitment and local H3K9 deacetylation. Conserved suppression effects of TRIM5α orthologs from multiple species on both HIV-1 and endo-retroelement HERV-K LTR activities have also been demonstrated. These findings provide new insights into the molecular mechanisms by which proviral latency is initially established and activatable proviruses are resilenced by histone deacetylase recruitment.

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Section: Conserved Suppression Effects Of Nonhuman Trim5α and Trimcyp...supporting

confidence: 92%

TRIM5α recruits HDAC1 to p50 and Sp1 and promotes H3K9 deacetylation at the HIV-1 LTR

Ran

Zhu

et al. 2023

Nat Commun

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“…2b ). This AP-1 activation by SPSB1 may be explained in part by a recent finding that the SPRY domain of RhTRIM5α is essential for AP-1 but not NF-κB activation 25 . In addition, because ubiquitination of heterogeneous nuclear ribonucleoprotein A1 (HnRNP A1) by SPSB1 induces the expression of Rac1B 26 , which in turn elevates mRNA expression of c-Jun N-terminal kinase 2 and c-JUN 27 , it is plausible that these events cooperate to achieve activation of AP-1-dependent transcription.…”

Section: Discussionmentioning

confidence: 97%

Robust Enhancement of Lentivirus Production by Promoter Activation

Suzuki

Yoshida

Takeuchi

et al. 2018

Sci Rep

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Lentiviral vectors are a valuable tool to deliver exogenous genes for stable expression in cells. While much progress has been made in processing lentiviral vector-containing culture medium, it remains to be explored how the production of lentiviral vector from producer cells can be increased. We initially found that co-expression of the SPRY domain-containing SOCS box protein 1 (SPSB1) promotes the production of human immunodeficiency virus type 1 (HIV-1) and lentiviral vector with increased expression of the Gag and envelope proteins and activation of the HIV-1 LTR and CMV promoter. The presence of AP-1, NF-κB and CREB/ATF recognition sites in these promoters prompted us to utilize human T-lymphotropic virus type 1 (HTLV-1) Tax for lentiviral vector production because Tax activates all these transcription factors. Co-expression of a small amount of Tax markedly increased both the expression of viral structural proteins in producer cells and release of lentiviral vector particles, resulting in a more than 10-fold enhancement of transduction efficiency. Of note, the Tax protein was not detected in the lentiviral vector particles concentrated by ultracentrifugation, supporting the safety of this preparation. Collectively, these results indicate that promoter activation in producer cells represents a promising approach to preparing high-titer lentiviral vectors.

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“…The RING domain-associated ubiquitin ligase activity is instrumental in the restriction mechanism, as it directs some viral components as well as TRIM5α itself to proteasomal degradation [ 20 , 21 ]. The RING domain also promotes the formation of K63-linked ubiquitin chains that play a role in the restriction process [ 22 , 23 ] and activate innate immune pathways mediated by NF-κB, AP-1 and IFN-I [ 24 , 25 , 26 , 27 ]. At its C-terminus, TRIM5α has a SPRY/B30.2 domain whose sequence determines retroviral target specificity, i.e., which viruses are inhibited [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Editing of the TRIM5 Gene Decreases the Permissiveness of Human T Lymphocytic Cells to HIV-1

Désaulniers

Ortiz

Dufour

et al. 2020

Viruses

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Tripartite-motif-containing protein 5 isoform α (TRIM5α) is a cytoplasmic antiretroviral effector upregulated by type I interferons (IFN-I). We previously showed that two points mutations, R332G/R335G, in the retroviral capsid-binding region confer human TRIM5α the capacity to target and strongly restrict HIV-1 upon overexpression of the mutated protein. Here, we used clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-mediated homology-directed repair (HDR) to introduce these two mutations in the endogenous human TRIM5 gene. We found 6 out of 47 isolated cell clones containing at least one HDR-edited allele. One clone (clone 6) had both alleles containing R332G, but only one of the two alleles containing R335G. Upon challenge with an HIV-1 vector, clone 6 was significantly less permissive compared to unmodified cells, whereas the cell clones with monoallelic modifications were only slightly less permissive. Following interferon (IFN)-β treatment, inhibition of HIV-1 infection in clone 6 was significantly enhanced (~40-fold inhibition). TRIM5α knockdown confirmed that HIV-1 was inhibited by the edited TRIM5 gene products. Quantification of HIV-1 reverse transcription products showed that inhibition occurred through the expected mechanism. In conclusion, we demonstrate the feasibility of potently inhibiting a viral infection through the editing of innate effector genes. Our results also emphasize the importance of biallelic modification in order to reach significant levels of inhibition by TRIM5α.

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Rhesus monkey TRIM5α protein SPRY domain contributes to AP-1 activation

Cited by 7 publications

References 71 publications

TRIM5α recruits HDAC1 to p50 and Sp1 and promotes H3K9 deacetylation at the HIV-1 LTR

TRIM5α recruits HDAC1 to p50 and Sp1 and promotes H3K9 deacetylation at the HIV-1 LTR

Robust Enhancement of Lentivirus Production by Promoter Activation

Editing of the TRIM5 Gene Decreases the Permissiveness of Human T Lymphocytic Cells to HIV-1

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